Fluticasone Furoate/Vilanterol: a Review of Its Use in Patients with Asthma

Abstract

Fluticasone furoate/vilanterol (Relvar(®)) is a once-daily, fixed combination of an inhaled corticosteroid (ICS) and a long-acting β2-adrenoreceptor agonist (LABA), delivered via a dry powder inhaler (Ellipta(®)). It is approved for the treatment of asthma in the EU and Japan, and is the first once-daily ICS/LABA to be available for this indication. Fluticasone furoate is an enhanced-affinity glucocorticoid receptor agonist, with potent anti-inflammatory activity. Vilanterol produces rapid and prolonged bronchodilation. In phase III trials in adolescents and adults with various levels of asthma uncontrolled on ICS and/or ICS/LABA, fluticasone furoate/vilanterol 100/25 or 200/25 µg once daily (approved dosages in the EU) significantly improved pulmonary function compared with placebo or equivalent dosages of fluticasone furoate alone (in some trials) or fluticasone propionate. In similar trials, fluticasone furoate/vilanterol 100/25 µg once daily was as effective as fluticasone propionate/salmeterol 250/50 µg twice daily in improving pulmonary function and significantly reduced the risk of severe asthma exacerbation relative to fluticasone furoate alone. In clinical trials, fluticasone furoate/vilanterol was generally well tolerated with fewer than 15 % of patients experiencing treatment-related adverse events, the most common of which were oral/oropharyngeal candidiasis, dysphonia, extrasystoles and cough. The tolerability profile of fluticasone furoate/vilanterol was generally similar to that of fluticasone propionate/salmeterol. Thus, fluticasone furoate/vilanterol is an effective and generally well tolerated ICS/LABA option for the treatment of uncontrolled asthma.

Phamacology of fluticasone furoate and vilanterol trifenatate combination therapy for asthma

“…An indirect bronchial challenge using adenosine 5ʹ-monophosphate (AMP) was performed at various time points after dosage. Single-dose FF and FP showed significant improvements in the provocative concentration of AMP producing a 20% decline (PC 20 AMP) in the forced expiratory volume in one second (FEV 1 [28]. This was the first study to show that FF clinically has a long duration of action, suggesting that it may be compatible with OD dosing.…”

“…New bronchodilators with a longer duration of action as once daily (OD) therapy have now been developed. Fluticasone furoate (FF) is a novel inhaled corticosteroid (ICS) with a 24-h duration of action while vilanterol trifenatate (VI) is an inhaled selective long-acting β 2 -agonist with fast-onset and prolonged bronchodilatation over 24 h. The combination of FF/ VI has been approved and used in chronic obstructive pulmonary disease as OD maintenance therapy [1][2][3]. This paper reviews the literature supporting the use of the combination of FF/VI as the OD maintenance treatment of asthma.…”

Spotlight on fluticasone furoate/vilanterol trifenatate for the once-daily treatment of asthma: design, development and place in therapy

“…The same year, the same combination of drugs, doses and delivery system (Relvar Ellipta ® ; GSK, UK) was approved in Japan and the European Union for the treatment of asthma 9. Breo Ellipta (FF [100 or 200 μg]/VI [25 μg]) was approved by the FDA for the maintenance treatment of asthma in April 2015 2.…”

Pharmacokinetics of Single and Repeat Doses of Fluticasone Furoate/Umeclidinium/Vilanterol in Healthy Chinese Adults

“…22 In vivo data showed that both FF 15 and VI 23 are metabolized primarily by the liver enzyme cytochrome P450 (CYP) 3A4; in contrast, neither CYP3A4 24 nor CYP2D6 25 is involved in UMEC clearance. Excretion is almost exclusively by feces for FF, 26 both urine and feces for VI, 20,26 and biliary secretion (and, to a lesser extent, in urine) for UMEC. 21 Two healthy-volunteer dose-finding studies evaluated the PK and pharmacodynamics of the individual components of FF/UMEC/VI administered as a triple combination compared with the dual combinations of FF/VI (Relvar/Breo ELLIPTA; GlaxoSmith-Kline plc, Middlesex, United Kingdom) or UMEC/VI (Anoro ELLIPTA; GlaxoSmithKline plc, Middlesex, United Kingdom) in non-Chinese participants.…”

“…In vivo data showed that both FF and VI are metabolized primarily by the liver enzyme cytochrome P450 (CYP) 3A4; in contrast, neither CYP3A4 nor CYP2D6 is involved in UMEC clearance. Excretion is almost exclusively by feces for FF, both urine and feces for VI, and biliary secretion (and, to a lesser extent, in urine) for UMEC…”